Evaluate the Efficacy and Safety of Irochel for the Management of Iron Overload in Thalassemia Patients in Comparison With Deferoxamine

Overview

This research study was an experimental, randomized, controlled clinical trial to evaluate the safety and efficacy of coded Unani formulation Irochel for the management of IOL due to repetitive blood transfusion in comparison with DFO in already diagnosed 132 transfusion-dependent thalassemia patients of both genders of 10 years to 16 years of age. The study was conducted at Hamdard Matab, Araam Bagh, where patients came from multiple thalassemia centers such as the Hussaini Blood Bank, National Institute of Blood Diseases (NIBD), Fatimid Foundation, Umair Sana Thalassemia Center, Kashif Iqbal Thalassemia Center, and Civil Hospital. The data was collected through the Clinical Record Form (CRF) and then analyzed by SPSS version 23. The study was conducted during the years 2014-2020. The study comprises two phases: 1) Development of Irochel and 2) Clinical Trials. The "Irochel" is a round, disk-shaped, black-colored, bitter, polyherbal formulation of 500 mg (tablet) with a characteristic odor. It consists of different ratios of extracts (hydroethanolic) of six medicinal herbs. The combined effect of these novel herbs was found to be potent in iron chelation and helps to improve the quality of life of thalassemia patients due to their high nutritional values and ethnopharmacological activities and their broad spectrum of therapeutic potential.

This experimental, randomized, controlled clinical trial evaluated the safety and efficacy of the coded Unani polyherbal formulation Irochel (IRC) for the management of iron overload (IOL) caused by repeated blood transfusions in transfusion-dependent thalassemia (TDT) patients, in comparison with Deferoxamine (DFO). A total of 132 diagnosed TDT patients of both genders, aged 10-16 years, participated in the study. The trial was conducted from 2014 to 2020 at Hamdard Matab, Araam Bagh, Karachi, with patients referred from several thalassemia centers, including NIBD, Fatimid Foundation, Umair Sana Thalassemia Center, Kashif Iqbal Thalassemia Center, Civil Hospital, and Hussaini Blood Bank. Data were collected using Clinical Record Forms (CRFs) and analyzed using SPSS version 23. The study comprised two phases: (1) development and preclinical evaluation of Irochel and (2) clinical evaluation in human subjects. Irochel is a 500-mg polyherbal tablet containing six medicinal plants. These herbs possess diverse phytotherapeutic and nutraceutical properties and contain bioactive compounds potentially relevant to iron chelation, antioxidant activity, and management of thalassemia-associated complications. During formulation development, the herbs were authenticated and subjected to organoleptic and pharmacognostical evaluation. Phytochemical screening demonstrated alkaloids, amino acids, carbohydrates, proteins, flavonoids, glycosides, saponins, tannins, and resins. The formulation was evaluated for cytotoxicity, antioxidant, antimicrobial, toxicological, and pharmaceutical properties. The brine shrimp lethality assay demonstrated an LC50 of 24.327 µg/mL, while DPPH analysis showed significant free-radical scavenging activity. Moderate antimicrobial activity was observed against Staphylococcus aureus. Acute and subacute toxicity studies indicated no major behavioral, gross pathological, or histopathological toxicity, although some hematological and biochemical parameters showed significant changes warranting further evaluation. Pharmaceutical quality-control testing confirmed satisfactory physical characteristics, including tablet weight, dimensions, hardness, friability, disintegration, granule uniformity, flow, lubrication, particle distribution, and manufacturing parameters. In the randomized clinical trial, 66 subjects were assigned to each group. The control group received DFO subcutaneously through a portable infusion device for 8-12 hours daily at 40-60 mg/kg body weight, while the test group received Irochel 500 mg twice daily orally with lukewarm milk. Baseline demographic characteristics, vital signs, BMI, and clinical findings were assessed. Following treatment, improvements were observed in general health and several systemic complaints in the Irochel group. Significant improvements were observed in several hematological parameters following Irochel treatment. The RBC count showed a highly significant within-group improvement (p=0.000), while the corresponding change in the DFO group was insignificant (p=0.321). Hb also showed a highly significant improvement in the Irochel group (p=0.000), whereas the DFO group showed an insignificant change (p=0.121). The WBC count showed a significant improvement in the Irochel group (p=0.031), while the control group showed no significant change (p=0.270). Platelet count also improved significantly in the Irochel group (p=0.001), compared with an insignificant change in the control group (p=0.849). ESR showed no significant change in the Irochel group (p=0.125), whereas a significant change was observed in the control group (p=0.002). The iron profile demonstrated significant changes following Irochel treatment. Serum iron showed significant improvement (p=0.030), while serum ferritin showed a highly significant change (p=0.000). In the DFO group, serum ferritin also showed a statistically significant within-group change (p=0.006). TIBC showed a significant change in the Irochel group (p=0.038), whereas the control group showed no significant change (p=0.635). Liver-function parameters, including total bilirubin, SGPT, GGT, and ALP, showed significant improvement following Irochel treatment. Lipid-profile analysis demonstrated a significant reduction in LDL (p=0.000). In contrast, the control group showed significant changes in total cholesterol (p=0.003), LDL (p=0.000), and triglycerides (p=0.000). Urinalysis showed improvement in several urinary parameters in the Irochel group, including RBCs, pus cells, crystals, and bacteria. Pearson correlation and linear regression analysis demonstrated a positive relationship between dominant body temperament and serum ferritin levels before and after treatment. A clinically important improvement was observed in transfusion dependency following Irochel treatment, with increased intervals between transfusions and reduced transfusion requirements. In contrast, transfusion dependency remained persistent in the DFO group. Irochel demonstrated good compliance and acceptability, with no reported adverse effects in the test group. In contrast, adverse effects were reported among DFO-treated subjects, including gastrointestinal and hepatobiliary complaints, bone pain, skin itching, swelling, and injection-site reactions. The Irochel group also did not require supportive medications, whereas DFO-treated subjects required various supportive therapies. Overall clinical assessment demonstrated marked, good, and slight improvement among Irochel-treated subjects, whereas the majority of subjects in the control group showed no improvement. The estimated annual treatment cost of Irochel was substantially lower than that of DFO/Desferal therapy in Pakistan. Overall, the findings indicate that Irochel demonstrated promising safety, acceptability, compliance, hematological and iron-profile benefits, improvement in liver and lipid parameters, reduced transfusion dependency, and potential cost-effectiveness compared with DFO. The study supports further well-designed and adequately powered clinical trials to confirm the efficacy and safety of Irochel for the management of transfusion-related iron overload in TDT patients.